Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes.

ABSTRACT

To evaluate changes in the inflammatory response of thioredoxin (TXN), thioredoxin interacting protein (TXNIP), transducer and activator of transcription 3, NFƙB-p50 and STAT3 at the level of maternal serum, placenta, and umbilical cord blood of women with gestational diabetes mellitus type 2 (GDMA2) compared to normal pregnancies (NP). Thirty pregnant women (20 with GDMA2 and 10 NP) were recruited during admission for delivery. Blood samples were obtained from the parturients and umbilical cords, as well as placental tissue for mRNA and protein extraction. TXNIP mRNA expression was significantly increased in maternal serum of women with GDMA2 compared to NP women. TXNIP mRNA was significantly decreased in GDMA2 placentas and cord blood compared to NP. TXN/TXNIP mRNA ratio showed significantly high absolute values in placental and cord blood (2.39 and 1.66) respectively, compared to maternal ratio (1.084) (P < 0.001). TXN/TXNIP placenta protein ratio showed similar values between GDMA2 and NP (0.98 and 0.86; P = 0.7). STAT3 and its target protein SOCS3, as well as NFƙB-p50 mRNA expression were significantly increased in placentas of GDMA2. NFƙB-p50 mRNA expression was significantly decreased in cord blood compared to both maternal and placental mRNA expression. Pro-inflammatory changes are expressed by low mRNA TXN/TXNIP ratio in maternal blood of GDMA2 patients, but not in placental and umbilical cord blood samples. This, as well as the feedback role of SOCS3 in STAT3 pathway and NFƙB-p50 expression, may indicate that the placenta has a role in protecting the fetus from damage due to inflammatory response, which is common in diabetes.